Cardiomyocyte ionic currents in intact young and aged murine Pgc-1β atrial preparations.

Introduction: Recent studies reported that energetically deficient murine Pgc-1β hearts replicate age-dependent atrial arrhythmic phenotypes associated with their corresponding clinical conditions, implicating action potential (AP) conduction slowing consequent upon reduced AP upstroke rates.

Materials And Methods: We tested a hypothesis implicating Na current alterations as a mechanism underlying these electrophysiological phenotypes. We applied loose patch-clamp techniques to intact young and aged, WT and Pgc-1β, atrial cardiomyocyte preparations preserving their in vivo extracellular and intracellular conditions.

Results And Discussion: Depolarising steps activated typical voltage-dependent activating and inactivating inward (Na) currents whose amplitude increased or decreased with the amplitudes of the activating, or preceding inactivating, steps. Maximum values of peak Na current were independently influenced by genotype but not age or interacting effects of genotype and age on two-way ANOVA. Neither genotype, nor age, whether independently or interactively, influenced voltages at half-maximal current, or steepness factors, for current activation and inactivation, or time constants for recovery from inactivation following repolarisation. In contrast, delayed outward (K) currents showed similar activation and rectification properties through all experimental groups. These findings directly demonstrate and implicate reduced Na in contrast to unchanged K current, as a mechanism for slowed conduction causing atrial arrhythmogenicity in Pgc-1β hearts.